Paul S. Frenette, MD
Director, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine
Hematology is embedded in me. As an intern at McGill University, I vividly remember going to the office of Dr. Phil Gold, chair of medicine at the Montreal General Hospital, to ask for his permission to attend the American Society of Hematology’s annual meeting in 1988 in Atlanta. Being from the French part of Canada, my English at the time was quite limited; I really had to muster up all my courage to enter the chairman’s office for this unusual request. Dr. Gold, a wonderful physician-scientist who had become famous for his discovery of the carcinoembryonic antigen, enthusiastically supported the idea and became my first mentor and role model during my residency. I had such a wonderful time that I have returned to ASH nearly every year for the science, of course, but also to catch up with my friends.
|Paul S. Frenette, MD
Despite (or perhaps owing to) my limited experience in the lab, I was very interested in basic science research. At the time, hematology/oncology training programs in Canada were clinically oriented, and thus I came to the United States in 1991 to enroll in the Tufts New England Medical Center Program, which was headed by Dr. Bruce Furie. There, I had the privilege to learn clinical hematology with Drs. Jane Desforges and Bob Schwartz, giants of the field. In the fall of 1991, I attended a seminar by Dr. Denisa Wagner on the generation of P-selectin knockout mice. This was the hot new technology. Impressed by its potential power, I thought it would be very important to learn the technique. I joined Dr. Wagner’s laboratory on a project to generate double-knockout mice lacking both P- and E-selectins in close collaboration with Dr. Richard Hynes at MIT. The project was extremely risky because the mice had to be generated from two rounds of homologous recombination of the cloned genomic DNA in embryonic stem cells, something that had never been done. If I had understood the difficulty and risks of the project, I probably would not have gotten involved. But I did, and, in the end, things worked out. Drs. Wagner and Hynes were a great collaborative team that basically brought me up as a scientist. As clinicians, we tend to be impatient and want to get results quickly. My first realization was that good research takes time, patience, and persistence.
Toward the end of my postdoctoral tenure, Dr. Barry Coller, who was the chairman of the Department of Medicine at Mount Sinai School of Medicine, came to Boston to give a seminar. After his seminar, he was interested in learning more about handling mouse platelets and our intravital microscopy studies. He asked me if he could watch me perform a tail vein injection in the basement of the old building where the Wagner lab was then located. Fortunately, despite my nervousness, I managed to properly inject into the mouse vein. This injection probably landed me my first faculty job.
Mount Sinai recruited me, through the Manhattan Sickle Cell Center headed by Dr. George Atweh, to evaluate the role of adhesion molecules in sickle cell disease using emerging mouse models. I knew nothing about red blood cells and thought it might be an interesting challenge. We used a genetically complex humanized mouse model that had been generated by Dr. Mohan Narla, who taught me a great deal about the disease, among other things. Following my recruitment, Dr. Atweh’s sage advice and mentoring were invaluable in these initial independent years to help me navigate through the difficulties of getting my first NIH grant. Although we had set out to investigate the adhesion mechanisms of sickle red blood cell (RBC) interactions with the endothelium in vivo in collaboration with Dr. Coller, we had observed that RBCs were mostly captured in vivo by leukocytes that were adherent in venules. This observation led us to investigate the role of the inflammatory response and pathological implications of these heterotypic interactions in thromboinflammatory diseases, a topic still active in my laboratory.
As a junior faculty member at Mount Sinai, I was fortunate to become an ASH Scholar Award winner. This award was critical in providing my burgeoning research program the additional funding and freedom to test new, perhaps more risky, ideas. During my last years as a research fellow at Harvard, I developed an interest in studying the mechanisms mediating hematopoietic stem cell trafficking between the bone marrow and blood compartments. Ultimately, this line of investigation has led us to make the unexpected observation that signals from the nervous system locally regulated the stem cell niche in the bone marrow. I am very proud that this work was selected for presentation at the ASH annual meeting Plenary Session each of the past two years. The dissection of the molecular and cellular constituents of the bone marrow niche represents another major area of ongoing research in the laboratory. I am extremely grateful for the dedicated students and postdoctoral fellows that have brought these projects and publications to fruition.
This July, I will be moving to Albert Einstein College of Medicine to become the first director of the Gottesman Institute of Stem Cell and Regenerative Medicine Research. I am excited to be given the opportunity to recruit several junior faculty members into the Institute. This will be a great way to expand my role as a mentor and give back to junior investigators.
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